Huntingtin-mediated axonal transport requires arginine methylation by PRMT6

The huntingtin (HTT) protein transports various organelles, including vesicles containing neurotrophic factors, from embryonic development throughout life. To better understand how HTT mediates axonal transport and why this function is disrupted in Huntington's disease (HD), we study vesicle-associated HTT and find that it is dimethylated at a highly conserved arginine residue (R118) by the protein arginine methyltransferase 6 (PRMT6). Without R118 methylation, HTT associates less with vesicles, anterograde trafficking is diminished, and neuronal death ensues—very similar to what occurs in HD. Inhibiting PRMT6 in HD cells and neurons exacerbates mutant HTT (mHTT) toxicity and impairs axonal trafficking, whereas overexpressing PRMT6 restores axonal transport and neuronal viability, except in the presence of a methylation-defective variant of mHTT. In HD flies, overexpressing PRMT6 rescues axonal defects and eclosion. Arginine methylation thus regulates HTT-mediated vesicular transport along the axon, and increasing HTT methylation could be of therapeutic interest for HD.Telethon-Italy and Autonomous Province of Trento (TCP12013 to M.P.); Association Française contre les Myopathies (AFM-22221 to M.P. and M.B.); PRIN-MUR (2017F2A2C5 to M.P.); National Institutes of Health (1R21NS111768-01 to M.P. and U.B.P.); PROGRAM RARE DISEASES CNCCS-Scarl-Pomezia (M.P.); FONDAZIONE AIRC-Italy (24423 to M.P.); Alzheimer Trento Onlus with the legato Baldrachi (M.B.); the Agence Nationale de la Recherche (ANR-15-JPWG-0003-05 JPND CIRCPROT and ANR-18-CE16-0009-01 AXYON to F.S.) and the Spanish Ministry of Science, Innovation and Universities (RTI2018-096322-B-I00 MCIU/AEI/FEDER-UE to J.J.L.

Mercury and selenium in the food web of Lake Nahuel Huapi, Patagonia, Argentina

Despite located far from point sources of Hg pollution, high concentrations were recorded in plankton from the deep oligotrophic Lake Nahuel Huapi, located in North Patagonia. Native and introduced top predator fish with differing feeding habits are a valuable economic resource to the region. Hence, Hg and Se trophic interactions and pathways to these fish were assessed in the food web of this lake at three sites, using stable nitrogen and carbon isotopes. As expected based on the high THg in plankton, mercury did not biomagnify in the food web of Lake Nahuel Huapi, as most of the THg in plankton is in the inorganic form. As was observed in other aquatic systems, Se did not biomagnify either. When trophic pathways to top predator fish were analyzed, they showed that THg biomagnified in the food chains of native fish but biodiluted in the food chains of introduced salmonids. A more benthic diet, typical of native fish, resulted in higher [THg] bioaccumulation than a more pelagic or mixed diet, as in the case of introduced fish. Se:THg molar ratios were higher than 1 in all the fish species, indicating that Se might be offering a natural protection against Hg toxicity.Fil: Arcagni, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Unidad de Actividad de Ingeniería Nuclear. Laboratorio de Análisis por Activación Neutróica; ArgentinaFil: Rizzo, Andrea Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Unidad de Actividad de Ingeniería Nuclear. Laboratorio de Análisis por Activación Neutróica; ArgentinaFil: Juncos, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Unidad de Actividad de Ingeniería Nuclear. Laboratorio de Análisis por Activación Neutróica; ArgentinaFil: Pavlin, Majda. Institute Jožef Stefan; EsloveniaFil: Campbell, Linda M. Saint Mary's University; CanadáFil: Arribere, Maria Angelica. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Unidad de Actividad de Ingeniería Nuclear. Laboratorio de Análisis por Activación Neutróica; ArgentinaFil: Horvat, Milena. Institute Jožef Stefan; EsloveniaFil: Ribeiro Guevara, Sergio. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Unidad de Actividad de Ingeniería Nuclear. Laboratorio de Análisis por Activación Neutróica; Argentin